Antibiotic and fungicidal agents

ABSTRACT

A process for controlling the growth of fungus comprising treating the fungus with a compound of the formula:   wherein A8 is lower alkylene, R8 is lower alkyl and Y8 is selected from the group consisting of hydrogen and methoxy.

United States Patent n 1 Gold et al.

[ Aug. 26, 1975 ANTlBlOTlC AND FUNGlClDAL AGENTS [75] Inventors: MarvinH. Gold, Sacramento; Henry J. Marcus, West Covina, both of Calif.

[73] Assignee: Aerojet-General Corporation, El Monte, Calif.

[22] Filed: Mar. 2, 1970 [El] Appl. No.1 15,942

Related US. Application Data [62] Division of Set. No. 487,942, May 20,I965, Pat, No, 3,513,243, which is a division of Ser. No. 326,286, Novv26, 1963, Pat. No 3,359,334,

OTHER PUBLICATIONS Chemical Abstracts, (l), 56; l4072b, (1962).

Chemical Abstracts, (ll), 59: l38l3c, ([963).

Chemical Abstracts, (Ill), 64: ll84h to ([966).

Primary Examiner-Jerome D, Goldberg Almrney, Agent, or FirmEdward O.Ansell [57] ABSTRACT A process for controlling the growth of funguscomprising treating the fungus with a compound of the formula:

wherein A, is lower alkylene, R, is lower alkyl and Y, is selected fromthe group consisting of hydrogen and methoxy.

3 Claims, N0 Drawings ANTIBIOTIC AND FUNGICIDAL AGENTS This applicationis a division of copending application Ser. No. 487.942. filed May 2().[965 now US. Pat. No. 3.513.243 which. in turn. is a divisionalapplication of Ser. No. 326.286. filed Nov. 26. I963. now US. Pat. No.3.359.334.

This invention relates to certain novel halo dinitro compounds and theirmethod of preparation.

It is an object of this invention to prepare certain novel organiccompounds. It is another object of this invention to prepare new nitrocompounds in a novel manner. Still another object of this invention isto provide novel antibiotic and antifungal compositions. These and otherobjects of this invention will be apparent from the detailed descriptionwhich follows.

One type of the novel compounds of this invention has the followinggeneral formula:

wherein R is a monovalent or divalent organic radical selected from thegroup consisting of:

I A, cH R.

wherein A, is a lower alkylene radical. preferably of from I to 6 carbonatoms and R, is a lower alkyl or lower whydroxy alkyl radical.preferably of from l to (1 carbon atoms;

ll A:-( 0- R.

wherein A is lower alkylene. preferably of from l to 6 carbon atoms andR is a lower alkyl radical of from l to 6 carbon atoms;

wherein A is an alkylene radical preferably having from to about carbonatoms;

wherein A is an alkylene radical. preferably from 1 to about 20 carbons;and R, and R. are the same or different and are selected from the groupconsisting of hydrogen. hydrocarbyl. preferably alkyl or aryl havingfrom I to about l2 carbons.

-h vdroxyalkyl preferabl v having from I to about 12 carbons.

wherein A are alkylene. preferably of from l to It) carbons;

wherein A.; and R.. are alkylene. preferably of from 1 to 20 carbons;

wherein the A groups are alkylene. preferably of from I to 20 carbons;and R is alkylene. preferably of from 1 to 20 carbons or vinylene CH CHI1 is an integer of from I to 2 and being equal to the valence of R; andX is chloro or bromo.

Illustrative compounds within the scope of Formula (I) include:

S-chloro-5.5-dinitro-2-hydroxy pentane.

6-bromo-6.b-dinitro-3-hy'droxy hexane.

S-bromo-5.5-dinitrol .Z-pentanediol.

l-chlorol .l -dinitro-Z-cyanoethane.

l-bromol l -dinitrovaleronitrile.

N-butyl-3 chloro-3.3-dinitropropionamide.

N-clecyl-S-chloro-S.5dinitropentanamide.

N-w-hydroxyethyl-4-dinitrobutyramide.

N.N-diethyl-4-chloro-4.4-dinitrobutyramide.

Z-chloro-Z.Z-dinitroethyl-(v-cMoro-6.6-

dinitrohexanoate. 4-chloro-4.4-dinitrobutyl-4-chloro-4.4

dinitrobutyrate.

l .3-bis-( 4chloro-4.4dinitrobutyryloxy )-propane.

l. l ()bis-(4-chloro-4.4-dinitrobutyryloxy )-decane.

l.8-bis-( 3-chloro-3.3-dinitropropionyloxy )-octane.

bis-( 3-chloro-3.3-dinitropropyl) adipate.

bis-( 3-chloro-3.3-dinitropropyl) maleate.

bis-( S-chloro-S.S-dinitropentyl) adipate.

his-(S-chloro-S.S-dinitropentyl) maleate.

bis-( 5-bromo-5.S-dinitropentyl) octanedioate.

bis-( S-bromo-S.S-dinitropentyl) maleate.

bis-(2-chloro-2,Z-dinitroethylJ dodecanedioate.

bis-( 2-chloro-2.2dinitroethyl) maleate.

In general. the compounds of Formula (I) are prepared by reactingchlorine or bromine with the corresponding salt of an organicgem-dinitro compound in accordance with the following general reaction:

the halo dinitro compounds of this invention are prepared according tothe following reaction equation:

(III) X- wherein X, A R and R, are as defined above and Z, is chloro.bromo or hydroxy.

When R is in Formula (I). the preparation is in accordance with thefollowing general reaction:

No no wherein X and A are as defined above and 7. is lower alkyl. i.e..from I to 6 carbons.

When R is o 0 II II in the above Formula (I). the reaction is asfollows:

No. 0 I II so, No,

wherein X. R and A. are as defined above and 2.; is hydroxy, chloro orbromo.

When R is III in Formula (I). the reaction scheme is in accord with thefollowing:

I II II C A UH ric da.

wherein X. A and R are as defined above and Z is hydroxy. chloro orbromo.

The above reaction is conveniently carried out in any inert polar ornon-polar solvent in which the reactants are soluble. i.e.. water.methanol, ethanol, benzene. chloroform. etc. The proportions of thereactants employed in the reaction are not critical. Normally,stoichiometrically equivalent amounts are used since this results in themost economical utilization of the reactants. The reaction temperatureshould normally be suffieiently high so that the reactants will dissolveto a substantial degree in the reaction medium. but in any event. thereaction temperature should be below the composition temperature of thereactant. Normally. the reaction is conducted at a temperature betweenabout -2UC and about +l2()C. The most preferred temperature is fromabout l 0C to about +5()C. Pressure is not critical in this reaction.Therefore, while any pressure can be used. the reaction is normally rununder atmospheric pressure. Agitation of the reactants such as bymechanical stirrer. while desirable in that it increases the reactionrate, is not necessary. The novel compounds of this invention may beisolated in conventional manner such as by extraction, distillationand/or filtration.

In the csterification reaction indicated above in Equations III to VI,it may be desirable in some cases in order to increase the reactionrate. to include in the reaction mixture :1 small. effective catalyticamount (0.] to about 20% by weight based on total weight of reactants)of an acid esterilication catalyst such as aluminum trichloride or polyphosphoric acid.

To more clearly illustrate our invention the following examples arepresented. It is to be understood, however. that these examples areintended merely as an illustrative embodiment of the invention. In theexamples. the percentages are by weight unless otherwise indicated.

EXAMPLE I Preparation of Bis-(2-Chloro-2.2-Dinitroethyl) Maleate To asolution of 83 g 2.2-dinitropropane-l .3-diol in 150 ml methanol at 0Cwas added. in portions. with shaking and hand-stirring. a cold solutionof 32.5 g potassium hydroxide in ISO ml methanol. The light yellowpotassium 2.2-dinitroethanol precipitated immediately. After standing inice for half an hour. it was filtered and washed well with coldmethanol. The wet filter-cake was suspended in 250 ml water. and. withgood stirring. chlorine introduced at 0 to 5C. After 40 minutes, all thesalt had disappeared and an oil had separated on the bottom of theflask. The mixture was light green; it was stirred for minutes longer.the oil separated and the aqueous phase extracted three times withdiethyl ether. The oil and ether solution were combined and dried oversodium sulfate. Removal of the solvent under vacuum left a very lightgreen. slightly lachrymatory oil. Distillation at 0.4 to 0.5 mm and 57.5to 60C yielded 41 g (0.24 mole) of 2-chloro-2.2- dinitroethanol. The2-chloro2.2-dinitroethanol is then reacted with 0.14 mole of maleic acidat 50 to 60C. The bis-(2-ch1oro-2.2-dinitroethyl) maleate is obtained ingood yields.

EXAMPLE 11 Preparation of Methyl 4-Chloro-4.4-Dinitrohutyrate A 500 mlround-bottom 3-neck flask was fitted with mechanical stirrer.thermometer. and dropping funnel. It was charged with 57.2 g (0.258mole) crude methyl 5-hydroxy-4.4-dinitropentanoate [Kl-tiger. Journal ofOrganic Chemistry 16. 162-163. (1951)] in 150 ml methanol. At 0 5Csolution of 6.8 g sodium (0.30 mole) in 90 ml methanol was addeddropwise over minutes. Stirring was continued for an additional minutes.The yellow sodium salt of methyl 4.4-

fall. while a slow stream of chlorine was introduced.

The oil was separated. and the aqueous phase was extracted once with 100ml. then with 40 ml diethyl ether. The combined extracts were washedwith 200 ml water. and dried over sodium sulfate. Following removal ofsolvent by evaporation. the residue was submitted to vacuumdistillation. Two fractions were collected:

1. b.p. 60 to 66 at 0.15 mm. 1.0 g, 11,, 1.4614

ll. b.p. 66 to 69 at 0.15 mm. 7.1 g. n,, 1.4615 Both were colorlessliquids. and were combined.

Elemental analysis: Calc'd for C.-.H N O..-C1: C. 26.58%; H. 3.12%. Cl.15.64%. Found: C. 26.52%; H. 3.38%; Cl. 16.75%.

EXAMPLE Ill 2-Bromo-2.2-Dinitroethyl 4-Bromo-4.4-Dinitrobutyrate To 5.0g of 4% oleum (prepared by adding 120 g of 30% fuming sulfuric acid to100 g of96% sulfuric acid) 2bromo-2.2-

was added 1.8 g (0.0050 M) dinitroethanol and 1.36 g (00050 M) methyl4-bromo-4.4-dinitrobutyrate. Both substances disture of the oil-bath wasraised to 75C and maintained there for 20 hours. The reaction mixturewas poured on ice with stirring; at nearly colorless. Waxy solidseparated. After thoroughly washing with water. the solid was left todry on a porous plate. The crude ester weight 0.50 g (22% m.p. 66 to72C. Recrystallization from diisopropyl ether gave colorless product.mp. 71 .5 to 73C.

Elemental analysis: Calcd for: C. 15.87%; H. 1.33%; N. 12.34%. Found: C.16.03%; H. 1.32%; N. 12.68%.

When the above example was repeated using 2-ch1oro-2.2-dinitroethano1and methyl 4-chloro-4.4- dinitrobutyrate (prepared according to Example11) in lieu of 2-bromo-2.Z-dinitroethanol and methyl4-bromo-4.4-dinitrobutyrate. respectively. 2-chloro-2.2-dinitroethyl-4-chlor0-4.4-dinitrobutyrate is obtained in goodyields.

EXAMPLE IV 4 Bromo-4.4-Dinitr0butyranilide Fifteen grams (0.058 M)4-bromo-4.4-dinitrobutyric acid and 30 milliliters (0.42 M) thionylchloride were refluxed for 45 minutes. The excess thionyl chloride wasremoved under vacuum. and the acid chloride re covered by distillation.A solution of 5.83 g (0.0212 M) of the 4-bromo-4.4-dinitrobutyrylchloride in 10 ml benzene was added gradually. over 45 minutes. to asolution of 372g (0.040 M) aniline in 7 ml benzene at reflux. Theprecipitate which formed when the aniline solution was added tended todissolve at the beginning. but complete solution was not attained. Themixture darkened as the reaction proceeded. The walls of the flask wererinsed with 5 to 10 ml fresh benzene. and re fluxing continued for 30minutes. After cooling. an attempt to extract the aniline hydrochloridewith water caused crystallization of the crude product in the separatoryfunnel. The anilide was dissolved with heating. The benzene solution.while still warm. was washed twice with water. boiled to remove waterazeotropically, and. after cooling. treated with an equal volume ofhexane. The crude product was filtered. washed with hexane. andair-dried. Wt. 4.8 g (68%) m.p. 116 to 121C. On standing. an additional0.3 g (m.p. to 126C) was collected from the mother liquor and wash. Thecrude. tan anilide (4.8 g) was recrystallized from 70. ml isopropanoland 30 ml water. and decolorized twice with charcoal. The product wasvery light yellow; wt. 2.9 g (corresponding to a 43% yield) mp. 133 to135C. A small sample. recrystallized again from aqueous isopropanol. wasstill light yellow and melted at 134 to 136C.

Elemental Analysis: Calc'd for: C. 36.16%; H. 3.04%; N. 12.65%: Br.24.05%. Found: C. 36.75%; H. 3.23%; N. 12.46%. Br. 24.34%.

When the above example is repeated employing ethylamine in lieu ofaniline and 4-chloro 4.4- dinitrobutyric acid in place of 4-bromo-4.4dinitrobutyric acid. N-ethyl-4-chloro-4.4- dinitrobutyramide isobtained.

EXAMPLE V 1.4- Bis 4- Bromo-4.4- Din itrobutyryloxy Butane4-Bromo-4.4-dinitrobutyryl chloride (5.22 g. 0.0203 M) was added to1.4-butanediol (0.79 g. 0.0088 M). The reaction mixture became hot. andhydrogen chloride was evolved. The clear biscous light yellow mixturewas placed in an oil-bath at 85 to C for 35 minutes; it was taken up inabout 10 ml benzene. and the product precipitated by the gradualaddition of 30 ml hexane. The colorless crystals were collected andwashed with hexane. wt. 4.0 g (76% m.p. 80 to 82C.

A small sample recrystallized twice (for elemental analysis) frombenzene-hexane melted at 84 to 86C. The main portion (3.6) wasrecrystallized once from bcnzene-hexane l:l wt. 3.l g (36% recovery].m.p. 84 to 86C.

Elemental analysis: Calcd for: C. 25.37%; H. 2.84%; N. 9.86%; Br.281471. Found. C. 26.15%; H. 3.00%; N. 9.59%; Br. 28387:.

When the above example is repeated using 4-chloro4.4-dinitrobutyrylchloride in place of 4-bromo-4.4-dinitrobutyryl chloride and ethyleneglycol in lieu of l.4-butanediol. a good yield of bis (4-chloro-4.4dinitrobutyryloxy )-ethane is obtained.

EXAMPLE Vl Bis-t 2-Bromo-2.2-Dinitroethyl) Adipate2-Bromo-2.2-dinitroethanol (5.5 g. 0.0255 M). adipyl chloride (2.2 g.0.012 M). and 2 drops of concentrated sulfuric acid were heated on thesteam bath.

Evolution of hydrogen chloride began almost immediately. After 45minutes. the reaction mixture was poured into ice and water. Theprecipitated ester was broken up in a mortar and washed with water. Theester was then slurried on a funnel with one normal sodium carbonatesolution, filtered. and washed well with water. Five and one-half gramsof crude product (m.p. 70 to 74C) were obtained after air drying. Theester was purified by dissolving in 25 ml benzene. charcoaling. andadding 35 ml hexane to the hot filtrate. Crystallization took place at20C. The adipate was filtered. washed with cold hexane. and dried;weight 4.5 g (7071 m.p. 72 to 74C. A small sample was againrecrystallized from benzenehexane for elemental analy sis (m.p. 74 to76C).

Calcd for: Br. 29.57%. Found: Br. 28.78%.

EXAMPLE V" Bis-t Z-Chloro-Z.Z-Dinitroethyl) AdipateZ-Chloro-2.2-dinitroethanol l l g. 0.065 M). adipyl chloride (5.5 g.0.030 M). and 4 drops of concentrated sulfuric acid were heated on thesteam-bath for 30 minutes. Evolution of hydrogen chloride began even onmixing in the cold. The light yellow solution was poured into ice andwater. The light tan semi-solid which resulted after a few minutesstirring could not be broken up into small particles in a mortar. It waswashed successively with water. one normal sodium carbonate solution,and again with water. as well as possible and left to dry on a porousplate. The crude ester l g. mp. 32 to 40C) was recrystallized from 35 mldiisopropyl ether. The mixture was chilled at 20C and the crystalscollected. washed with cold solvent. and dried: weight 6.0 g. m.p. 38 to48C. A small sample was again recrystallized from diisopropyl ether(m.p. 49 to lC) and submitted for elemental analy sis:

Calcd for: Cl. l5.73'/r. Found: Cl. lo.092?.

The main portion of the ester was recrystallized a second time fromdiisopropyl ether ml). and 3.8 g (28% of the product. mp. 47 to 52C.collected.

When the above example was repeated using sebacic acid in lieu of adipylchloride. bis-(2-chloro-2.2- dinitroethyl) sebacicate was obtained.

EXAMPLE Vlll Preparation of l-Chloro-l.l-Dinitrobutyronitrile To l moleof l.l-dinitrobutyronitrile (prepared by the addition of one moleofdinitromethane to one mole of acrylonitrile) is added 1 M potassiumhydroxide at about 40 to 50C. to form the potassium salt of LI-dinitrobutyronitrile. About grams of the salt is then dissolved in about2 liters of water. Then 100 ml of this aqueous solution is charged to a300 ml roundbottom 3-neck flask fitted with stirrer. thermometer and gasinlet tube. At 0 to 10C. chlorine gas is introduced with stirring. Theaddition of chlorine is continued for about 0.5 hour. The water isremoved by evaporation under vacuum. The product 1chloro-l .l-dinitro-3-cyano propane is obtained in good yields.

When the foregoing example is repeated utilizing l. ldinitro-B-methyI-butyronitrile in lieu of l.lbutyronitrile. l-chlorol l-dinitro-3-methylbutyronitrile is obtained.

EXAMPLE IX Preparation of 5-Chloro-5 5-Dinitrol .Z-Pentanediol To l moleof 5.5-dinitro-l.Z-pentanediol (prepared by the addition of l mole ofhydrogen peroxide to l mole of 5.5.5-trinitro-l.2-pentanediol) is addedI M potassium hydroxide at about 40 to 50C to form the potassium salt of5.5-dinitro-l.Z-pentanediol. About I00 grams of the salt is thendissolved in about 2 liters of water. Then I00 ml of this aqueoussolution is charged to a 300 ml round-bottom 3-neck flask fitted withstirrer. thermometer and gas inlet tube. At 0 to l0C. chlorine gas isintroduced with stirring. The addition of chlorine is continued forabout 0.5 hour. The water is removed by evaporation under vacuum. Theproduct 5-chloro-5.5-dinitro-l,Z-pentanediol is ob tained in good yield.

When the foregoing example is repeated utilizing 5,5-dinitro-2 pentanolin lieu of 5.5-dinitro-l.2- pentanediol. S-chloro-S,5-dinitro-2-pentanolis obtained.

in addition to the novel compounds within the scope of Formula (I) arestill another class of novel polynitro compounds. The compounds have thefollowing general formula:

N0 0 l ll (VII) R,.('- A,.-()-(Y,.

l Mo wherein A is a lower alkylene group preferably having from l toabout 6 carbon atoms such as methylene. ethylene. b utylene andhexamethylene; R is a lower alkyl group preferably having from l to 8carbons such as ethoxy (OC- H,-.). methoxy (OCH;;). etc.

Typical of the compounds within the scope of Formula [Vll] are:2.2-dinitrobutyl formate. 3.3- dinitrooctyl form-ate. 5.5-dinitrohexylformate. ethyl-2.2-dinitropropyl carbonate. hexyl-4.4-

dinitrodecyl carbonate. isopropyl-ZQ-dinitropropyl carbons and propyllZ-dinitropropyl carbonate.

The novel esters of the above formula are prepared in accordance withthe following general reaction:

1 h.p. to we 0.6 mm 1.4 g m, 1.4485 ll 73 to 76C 0.4 to 0.5 7.8 g [.4486

9.0 g. 54% lll "1C ().4 to 0.35 [.1 g l.4487

0 0 9 The residue (0.7 g) was slightly viscous and light brown ll l IIno, so.

wherein A,.. R and Y,. are as defined above; and 7... is hydroxy orhalogen. preferably chlorine or bromine.

The above reaction is conveniently. although not necessarily carried outin any inert solvent in which the reactants are soluble. i.e.. benzene.toluene or hexane. The proportions of the reactants employed in thereaction are not critical. Normally. stoichiometrically equivalentamounts are used siricc this results in the most economical utilizationof the reactants. Thus. usually l mole of alcohol is used per mole ofacid or halo carbonate. The reaction temperature should normally besufficiently high so that the reactants will dissolve to a substantialdegree in the reaction medium. but in any event. the reactiontemperature should be below the composition temperature of the reactant.Normally. the reaction is conducted at a temperature between about 0 andabout 100C. The most preferred temperature is from about +40 to about75C. Pressure is not critical in this reaction. Therefore. while anypressure can be used. the reaction is normally run under atmosphericpressure.

The above reaction is preferably conducted in the presence of aneffective catalytic amount of an acid esterification catalyst such asaluminum chloride or boron trifluoride.

EX AMPLE X 2.2-Dinitropropyl Form-ate To a solution of 16.0 g (0.10 M.95% pure) 2.2- dinitropropanol in 22 ml formic acid (98 to 10071 wasadded a spatula-tip of anhydrous aluminum chloride. After refluxing for23 hours. the mixture was poured into ice-water and the crude esterseparated with the aid of 30 ml methylene chloride. The organic phasewas extracted first with 50 ml. and then with 25 ml of cold one normalsodium hydroxide solution. washed twice with water. and dried overnight.Removal of the solvent in vacuo left 2.0 g l 1% of theory) of very lightgreen liquid. o l.4486. Distillation at 715 to 73.5C/0.6 mm gave acolorless distillate. n,,-"" 1.4487.

Elemental analysis: Calcd for C,,H..N- ,O,.: C. 26.97; H. 3.40; N.15.73. Found: C. 27.33". H. 3.37; N. 15.60.

When the foregoing example is repeated substituting 3.3-dinitrobutanolfor 2.2dinitropropanol. a good yield of 3.3-dinitrobutyl formate isobtained.

EXAMPLE Xl Methyl 3.. Dinitropropyl Carbonate To 50 ml of a benzenesolution of 2.2- dinitropropanol (containing about 0.08 M of thealcohol) was added 9.0 ml (0.12 M) methyl chloroformatc and aspatula-tip of anhydrous aluminum chloride. This mixture was refluxed 17hours. and the bcnyene and unreacted chloroformate removed in vacuo. Alight brown residue. consisting of much liquid and a little solidmatter. remained. The liquid was dissolved in chloroform. clarified withcharcoal. and the solvent removed. Fourteen grams of light brown liquid.11,, 1.4481. were obtained. Vacuum distillation yielded the followingfractions:

in color. The crude carbonate (Fractions 1. 11 and 111 combined) wasdissolved in 25 ml methylene chloride. It was extracted twice with coldsolutions of 20 and 10 ml. respectively. of one normal sodium hydroxide.washed twice with water. and dried over sodium sul fate. The carbonateafter removal of the solvent weight 4.8 g. n,,'-" 1.4422. On vacuumdistillation. the following fractions were collected:

l 88 to 93% 0.0 mm l.o g n,,'-'" 1.4423 ll 93 to 94C 0.6 mm 1.4 g n,,'-"l 4425 I11 94C 0.6 mm 0.1 g

Fraction ll showed no presence of hydroxyl in the infrared spectrum.

Elemental analysis (ll): Calcd for C -.H,.N O C. 28.85%; H. 3.8771; N.13.46%. Found: C. 29.49%; H. 4.37'71;N.l3.92'/1.

When the above example is repeated using 3.3-dinitro-l-pentanol in lieuof 2.2-dinitropropanol. and ethyl bromoformate in place of methylchloroformate. a substantial quantity of essentially pure ethyl-3.3-dinitropropyl carbonate is obtained.

The compounds of this invention. which contain a plurality of nitrogroups. are inherently useful as high explosives. These compounds canalso be used in any conventional explosive missile. projectile. rocketor the like. as the main explosive charge. An example of such a missileis described in US. Pat. No. 2.470.162. issued May 17. 1949. One way ofusing such high explosives in a device such as that disclosed in U.S.Pat. No. 2.470.162 is to absorb the liquid explosive in an absorbentmaterial such as cellulose. wood pulp. or sawdust. The resultantdynamite-type explosive can then be packed into the warhead of themissile. A charge thus prepared is sufficiently insensitive to withstandthe shock entailed in the ejection ofa shell from a gun barrel or arocket launching tube under the pressure developed from ignition of apropellant charge. and can be caused to explode on operation of animpact or timefuse mechanism firing a detonating explosive such as leadazide or mercury fulminate.

Certain of the novel compounds of this invention are also useful asfungicides. in the prevention of bacterial growth. and as plasticizersfor solid rocket propellant formulations.

This example describes a particular method of pre paring a novelpropellant composition from the following ingredients employing methyllldinitropropyl carbonate as a plasticizer:

EXAMPLE X11 EXAMPLE Xll -Continued Ingredient eight Percent Copperchromite (LSO Phenyl hetanaphth laminc (L21) Ferric acetylacctonate (MINGlycerol monoricinolcate lllt) Polypropylene glycol (M.W. ZlltlllIltlls-t Dioctyl u/clutc 3.01) Methyl ZJ-dinilropropyl carbonate (Ill)Lecithin 0.21) 'l'olylcnc diisocyunatc [.98

loom) The aluminum powder is stirred into about one-third of therequired volume of polypropylene glycol and glycerol monoricinolcate.The mixture is prepared in a stainless steel container. using acopper-beryllium spat ula. Mixing is continued for about It) minutes.

The aluminum slurry is added to a conventional mixer equipped withfacilities for heating, cooling and vacuumizing the propellant mix. Thewalls of the aluminum slurry container are scraped thoroughly. Thecontainer is rinsed with one-half of the required volume of dioctylazelate and the rinses are added to the mixer. The remainingpolypropylene glycol is added to the mixer. The methyl 2.2-dinitropropylcarbonate is mixed with the remaining dioctyl azelate until homogeneousand the solution is then added to the mixer.

With the mixer off, the ferric acetylacetonate. phenylbetanaphthylamine. and lecithin are added through a 4(l-mesh screen. Thecopper chromite is added to the mixer.

The mixer is covered and mixed by remote control for IS minutes under 26to 28 inches of vacuum. after which it is stopped and the vacuumreleased with dry nitrogen. The cover is removed from the mixer and theoxidizer is added by remote control with the mixer blades in motion.

After all of the oxidizer has been added. the mixer is stopped andscraped down. The propellant mass is mixed for 15 minutes at 70F under26 inches vacuum by remote control. The mixer is stopped and the vacuumreleased with dry nitrogen. The tolylene diisocyanate is added. afterwhich the mass is mixed for ll) minutes at 70F and 26 inches of vacuumby remote control. The vacuum is then released with dry nitrogen and themixture is cast.

Propellants prepared in the foregoing manner have a specific impulse inthe range from 225 to about 250 seconds.

The compounds of Formula (I) are especially useful as antibiotics and asanti-fungals. In this respect. the compounds of Formula (I) wherein X ischloro are far superior in effectiveness to the corresponding bromocompounds. Most preferred of the compounds within the scope of Formula(I) are those of the formula:

lIX)

wherein A,, is a lower alkylene group preferably having from l to about6 carbons. R. is a lower alkyl radical preferably having from I to about6 carbons and X is hydrogen or nitro. Typical compounds within the scopeof Formula (X) include Z-nitropropyl 2.2.3.3- tetrafluoro propyl etherand 2.2-dinitropropyl 2.2.3.3- tetrafluoro propyl ether. The compoundsof Formula (X) and their method of preparation are disclosed in greaterdetail in Assignee's copending U.S. application Ser. No. 326.284. filedNov. 26. 1963. now U.S. Pat. No. 3.399.240.

Other classes of compounds which can be used as antifungals according toour invention are:

N(.). o o No.

I ll It I No. No

wherein both A groups are lower alkylene from 1 to about 6 carbons. andthe R groups are alkyl of from 2 to 6 carbons;

(Xlll wherein Z, is:

wherein both R groups are lower alkyl. preferably of from i to 6carbons; and

wherein R in each instance is lower alkyl of from 1 to about 6 carbons.

The compounds of Formula (XI). and their method of preparation aredisclosed in Assignees copcnding U.S. application Ser. No. 326.287.filed Nov. 26. I963 now abandoned.

The compounds of Formula (XII). and their method of preparation aredisclosed in Assignees copending U.S. application Ser. No. 326.285.filed November 26. 1963 now U.S. Pat. No. 3.49231 l.

The compounds of Formulae (XIII) and (XIV). and their method ofpreparation are disclosed in Assignees copending US. application Ser.No. 326.288. filed Nov. 26. I963. now US. Pat. No. 3.306.929.

In the anti-bacterial test a compound within the scope of Formula (I)was compared in vitro to pencillin against B. subtillis (gram positivebacteria) and to chloromycetin against coli (gram negative bacteria).The compound tested was the compound of Example II. methyl4-chloro-4.4-dinitrobutyrate EXAMPLE XIII Two glass plates wereuniformly and completely coated with a sterile aqueous solution of gumagar pH 5.7. The agar film was inoculated with the B. subtillis. Uponeach plate was then placed a small 0. ll) ml glass cylinder. one filledwith a standard solution of penicillin containing 0.001 mg permilliliter. on the other plate an aqueous solution of themethyl-4-chloro-4.4- dinitrobutyrate containing one mg per milliliterThe plates were then incubated by maintaining them at a temperature ofabout 37C. After about 15 hours a clear zone of growth inhibition aroundeach of the cylinders could be observed. The area of the zone of growthinhibition around the cylinder containing methyl 4-chloro4.4-dinitrobutyrate was somewhat greater than the area of the zone ofgrowth inhibition around the cylinder containing the standard penicillinsolution.

EXAMPLE XIV Two glass plates were uniformly and completely coated with asterile aqueous solution ofgum agar. The agar film was inoculated withthe [:1 (U/f. Upon each plate was then placed a small glass cylinder.one filled with a standard solution of penicillin containing one unitper milliliter. on the other plate an aqueous solution of themethyl-4-chloro-4.4-dinitrobutyrate. The plates were then incubated at atemperature of about 37C. After about 15 hours a clear 7one of growthinhibition around each of the cylinders could be observed. The area ofthe zone of growth inhibition around the cylinder containingmethyl-4-chloro-4.4- dinitrobutyrate was somewhat greater than the areaof the zone of growth inhibition around the cylinder containing thestandard pencillin solution.

Anti-fungal tests were conducted using compounds within the scope ofFormulae (IX) to (XIV). In each of these tests the test organism wastrichophyton mentagrophytes.

EXAMPLE XV The drug was placed on the surface of an inoculated agarplate prepared in accordance with Example XIV. and the ZOHC ofinhibition caused by the test compound (().l mg/rnl) compared with thatproduced by a solution of undecylenic acid. (1).! mg/ml). a standardcommercial fungicide. The results of the testing are evaluated inaccordance with the following scale.

SCALE (J Inactive l Poor, (less active than undecylenic acid) 2 Good.(approximately equal to undecylenic acid) 3 Excellent. (at least 2.5times more active than undecylenic acid) The results obtained inaccordance with the abovedescribed anti-fungal tests are set forth inthe following table.

Bis-l I-bronio-ll-dinitrocthy l) adipatc Application of theantibacterial and antifungal compounds of this invention for the variouspurposes disclosed may be made from solutions in suitable solventcarriers. such as alcohol. benzene, and petroleum naphtha. or fromdispersions in aqueous or other media. or in the form of a dust. Theymay be used in combination with supplementary agents, such as talc.bentanite. tricalcium phosphate. various clays. spreadingagents-stickers and other adjuvants commonly used in bacteria and funguscontrol compositions. They may also be used in combination with otherbacteria and fungus control agents. such as sulfur fungicides or organicfungicides and various other agents commonly used in fungicidal andinsecticidal applications. When the bactericides and fungicides of thisinvention are used in conjunction with adjuvants. the active ingredientis employed in a bactericidally or fungicidally effec tive amount.normally from about (Hi1 to 90% by weight of the total composition.Caution should be used in using these products since many of them areirritant to the skin.

It will be understood that various modifications may be made in thisinvention without departing from the spirit thereof or the scope of theappended claims.

We claim:

I. A process for controlling the growth of fungus comprising applying tosaid fungus a compound of the formula:

wherein A is lower alkylene. R, is lower alkyl and Y is selected fromthe group consisting of hydrogen and methoxy in an amount effective toinhibit fungus growth.

2. A process for controlling the growth of fungus. said processcomprising applying to said fungus 2.2- dinitropropyl formate in anamount effective to inhibit fungus growth.

3. A process for controlling the growth of fungus. said processcomprising applying to the fungus methyl 2.2-dinitropropyl carbonate inan amount effective to inhibit fungus growth.

1. A PROCESS FOR CONTROLLING THE GROWTH OF FUNGUS COMPRISING APPLYING TOSAID FUNGUS A COMPOUND OF THE FORMULA:
 2. A process for controlling thegrowth of fungus, said process comprising applying to said fungus2,2-dinitropropyl formate in an amount effective to inhibit fungusgrowth.
 3. A process for controlling the growth of fungus, said processcomprising applying to the fungus methyl 2,2-dinitropropyl carbonate inan amount effective to inhibit fungus growth.